Mitonuclear epistasis involving TP63 and haplogroup Uk: Risk of rapid progression of knee OA in patients from the OAI

To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA). A total of 1095 subjects from the Osteoarthritis In...

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Published in:Osteoarthritis and cartilage 2024-05, Vol.32 (5), p.526-534
Main Authors: Durán-Sotuela, Alejandro, Oreiro, Natividad, Fernández-Moreno, Mercedes, Vázquez-García, Jorge, Relaño-Fernández, Sara, Balboa-Barreiro, Vanesa, Blanco, Francisco J., Rego-Pérez, Ignacio
Format: Article
Language:English
Subjects:
Disease Progression
DNA, Mitochondrial - genetics
Epistasis, Genetic
Genome-Wide Association Study
Humans
Knee Joint
Knee osteoarthritis
Mitonuclear epistasis
mtDNA variation
Osteoarthritis, Knee - epidemiology
Osteoarthritis, Knee - genetics
Rapid progression
Transcription Factors - genetics
Tumor Suppressor Proteins - genetics
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Summary:To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA). A total of 1095 subjects from the Osteoarthritis Initiative, with a follow-up time of at least 48-months, were included. Appropriate statistical approaches were performed, including generalized estimating equations adjusting for age, gender, body mass index, contralateral knee OA, Western Ontario and McMaster Universities Osteoarthritis Index pain, previous injury in target knee and the presence of the mtDNA variant m.16519C. Additional genomic data consisted in the genotyping of Caucasian mtDNA haplogroups and eight nSNPs previously associated with the risk of knee OA in robust genome-wide association studies. The simultaneous presence of the G allele of rs12107036 at TP63 and the haplogroup Uk significantly increases the risk of a rapid progression of knee OA (odds ratio = 1.670; 95% confidence interval [CI]: 1.031–2.706; adjusted p-value = 0.027). The assessment of the population attributable fraction showed that the highest proportion of rapid progressors was under the simultaneous presence of the G allele of rs12107036 and the haplogroup Uk (23.4%) (95%CI: 7.89–38.9; p-value 
ISSN:1063-4584
1522-9653
DOI:10.1016/j.joca.2023.12.008